The regulation of cyclic 3',5'-nucleotide phosphodiesterase and adenylate cycase from brain by calcium and a calcium-binding protein (the calcium-dependent regulator, CDR) will be investigated. The relative Ca2 ion concentration dependence of the two enzyme activities will be determined as a function of CDR concentration. The reaction kinetics of the CDR-dependent adenylate cyclase from brain will be characterized and the tissue distribution of the enzyme determined. Relationships between the Ca2 ion -dependent phosphodiesterase and various membrane-bound and cytoplasmic phosphodiesterases will be sought by physical comparisons on gel filtration chromatography, gel electrophoresis, and sucrose density ulcentrifugation, by comparison of reaction kinetics, and by cross reactivity of phosphodiesterase to antibody prepared to the Ca2 ion-dependent enzyme. The effects of drugs, such as the phenothiazine antipsychotics, on these enzymes and on the binding of CDR to membranes will be characterized. A common CDR binding subunit will be sought for the two enzymes.